A project to develop the complete immunophenotype of memory B cell has been initiated. This is being done evaluating normal subjects and patients with specific immune disorders including ALPS and CGD. In addition, the immunophenotypic data is being compared with single B cell Ig gene somatic hypermutation results generated in Dr. P. Lipsky's laboratory (NIAMS). These investigations have established that CD27 expression is altered in CGD and this appears to be a direct product of the defective oxidase activity as reflected by the link between CD27 expression and the proportion of normal cells in X-linked carriers. In addition, CD27 expression is markedly diminished in ALPS that may be related to some extent to protein cleavage from the cell surface based on increased levels of soluble CD27 found in the plasma of ALPS patients. Recent findings suggest that memory B cell levels are normal in CGD based on normal frequency of somatic hypermutation in B cells despite the marked decrease in CD27 expression on the B cells. This contrasts with a virtual absence of memory B cells using the same indicator system in ALPS patient's B cells and the over expression of certain families among the diminished memory B cells in ALPS suggesting B cell repertoire skewing that may be associated with the autoimmunity seen in this disorder. These studies suggest that the Fas pathway may be critical in the generation of memory B cells while defective NADPH oxidase activity does not impact memory B cell development but does diminish CD27 expression. These studies also point out the CD27 is not a consistently reliable marker of memory B cells in humans.